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At least 19 recordsLinked to original sources

PubMed1993

Molecular and biological characteristics of avian polyomaviruses: isolates from different species of birds indicate that avian polyomaviruses form a distinct subgenus within the polyomavirus genus.

The isolation and characterization of two avian polyomaviruses, from chicken (BFDV-2) and a parrot (BFDV-3), is reported. Both isolates are closely related to the non-mammalian polyomavirus budgerigar fledgling disease virus (BFDV) isolated from budgerigars (now called BFDV-1), and all three viral genomes are shown to have the same basic size of 4981 bp. A 151 bp insertion was, however, observed in the non-coding region of BFDV-2 which represented an exact duplication of the left half of the non-coding region, including the putative early promoter and amino terminus of the large T antigen. With a further 15 base pairs exchanged elsewhere throughout the three genomes, these viruses have distinct degrees of tropism for various avian species. The production of antibodies directed against a beta-galactosidase-large T antigen fusion protein of BFDV-1 is described. These antibodies detected the large T antigen, with an M(r) of approximately 80K, and the small t antigen, with an M(r) of approximately 24K, in cells infected with BFDV isolates. Whereas these antibodies bind with low affinity to the large T antigen of simian virus 40 (SV40), SV40- or mouse polyomavirus-specific antibodies will not bind to the BFDV large T antigen. Antibodies directed against BFDV structural polypeptides exhibit broad, reciprocal cross-reactivities with all three structural proteins of mammalian polyomaviruses. The significance of polyomavirus infections in various avian species is discussed. Based on unique structural and biological properties we propose that these viruses should be placed in a distinct subgenus (Avipolyomavirus) within the polyomaviruses.

Animals↗

PubMed1996

A short peptide eluted from the H-2Kb molecule of a polyomavirus-positive tumor corresponds to polyomavirus large T antigen peptide at amino acids 578 to 585 and induces polyomavirus-specific immunity.

A short peptide in complex with the H-2Kb molecule on PyRMA, a polyomavirus transfectant of the mouse lymphoma cell line RMA, was identified as a polyomavirus tumor-specific transplantation antigen. The peptide was obtained by affinity chromatography, acidic extraction, and reverse-phase high-pressure liquid chromatography (HPLC). In one HPLC fraction, a peptide sequence in which 5 of 8 amino acids, GKxGLxxA, corresponded to residues 578 to 585 of polyomavirus large T antigen was identified. In tumor rejection assays, we therefore tested three related synthetic peptides, corresponding to the octapeptide LT 578-585, GKTGLAAA; the nonapeptide LT 578-586, GKTGLAAAL; and the decapeptide LT 578-587, GKTGLAAALI. The octapeptide was found to give the most effective immunization against the outgrowth of the polyomavirus DNA-positive PyRMA tumor. However, none of the three peptides immunized against the original polyoma-virus-negative RMA line.

Amino Acid Sequence↗

PubMed1989

Characterization of a new polyomavirus (Polyomavirus papionis-2) isolated from baboon kidney cell cultures.

Viruses with papovavirus morphology were seen in fluids from baboon kidney cell cultures on three separate occasions (isolates A, B, and C). The size of the virions, 47.9 nm, placed the virus in the polyomavirus genus. It grew well in baboon kidney and Vero cells and less well in human embryo lung (HEL) fibroblasts. The virus could not be identified as the previously described baboon polyomavirus, SA 12, or as any of the other known primate polyomaviruses BK, JC or SV 40, the non-primate viruses mouse polyoma, K, rabbit kidney vacuolating virus (RKV) or bovine polyomavirus (FRKV) by immunofluorescence, immune electron microscopy or hemagglutination inhibition (HI) tests. A rabbit antiserum to the new virus (isolate A) reacted only with the three isolates and not with the other primate polyomaviruses studied. Thirteen percent of 118 wild-caught baboons (Papio anubis) had HI antibody to the new polyomavirus and 21 percent were seropositive for SA 12; only two baboons had antibody to both viruses. These results suggest that in baboons there are two antigenically distinct polyomaviruses which circulate independently. The two viruses may also be distinguished by their hemagglutinating properties: SA 12 agglutinated erythrocytes from a wider range of species but only the newly recognized polyomavirus agglutinated baboon erythrocytes. We propose that the two baboon viruses, SA 12 and the new virus, should be named Polyomavirus papionis-1 and Polyomavirus papionis-2 respectively.

Animals↗

PubMed1987

Anti-idiotypic antibodies to a polyomavirus monoclonal antibody recognize cell surface components of mouse kidney cells and prevent polyomavirus infection.

Anti-idiotypic antibodies have been successfully used to identify and isolate the receptor for several cell ligands. To prepare an immunologic probe for identification of the polyomavirus receptor on mouse kidney cells, polyclonal antisera against antipolyomavirus antibodies were prepared in rabbits. Fab fragments of the previously characterized monoclonal antibody E7, which neutralizes polyomavirus infection, were used for immunization (S. J. Marriott and R. A. Consigli, J. Virol. 56:365-372, 1985). Sera containing the greatest anti-idiotype activity were identified by enzyme-linked immunosorbent assay (ELISA) and purified by a series of affinity columns. The anti-idiotypic antibodies recognized the E7 idiotope in an ELISA, and anti-idiotype binding could be inhibited by preincubation of E7 monoclonal antibody with polyomavirus virions. When mixed with anti-idiotype immunoglobulin G (IgG), E7 was no longer capable of binding or immunoprecipitating polyomavirus virions or neutralizing polyomavirus infection. Direct immunofluorescence showed anti-idiotype IgG reactivity with a cell surface component of mouse kidney cells. Anti-idiotype F(ab')2 effectively competed with polyomavirus for binding to mouse kidney cells and displayed binding kinetics similar to those of polyomavirus. Virus infection of mouse kidney cells was blocked in a dose-dependent manner following treatment of the cells with anti-idiotype IgG. The anti-idiotype identified several proteins (95, 50, and 24 to 31 kilodaltons) in an immunoblot of mouse kidney cell membrane proteins but reacted predominantly with a single 50-kilodalton protein in a radioimmunoassay. The anti-idiotype failed to react with virus proteins in three assays, including ELISA, immunoprecipitation, and immunoblotting. The implications of this work for future identification and characterization of the polyomavirus receptor on mouse kidney cells are discussed.

Animals↗

PubMed1999

Use of the baculovirus system to assemble polyomavirus capsid-like particles with different polyomavirus structural proteins: analysis of the recombinant assembled capsid-like particles.

The genes encoding the structural proteins (VP1, VP2 and VP3) of murine polyomavirus were cloned into the p2Bac dual multiple cloning site vector, individually or jointly, and the corresponding proteins were expressed in Spodoptera frugiperda (Sf9) insect cells by cotransfecting Sf9 cells with the constructed vector and the linear DNA of Autographa californica multiple nuclear polyhedrosis virus (AcMNPV). Recombinant capsid-like particles could be purified 5 days post-infection from Sf9 cells infected with AcMNPV-VP1, with or without the involvement of minor protein (VP2 or VP3). Although VP2 and VP3 alone could not generate recombinant particles, they became incorporated into these particles when expressed with VP1 in Sf9 cells. Recombinant particles with different polyomavirus structural protein(s) were obtained by using different combined expression of these proteins in Sf9 cells. Cellular DNA of 5 kbp in size was packaged in all of the recombinant particles, which showed the same diameter as that of native virions. Agarose gel electrophoresis indicated that DNA packaged in these recombinant particles had a different pattern than that of native virions. Two-dimensional gel electrophoresis of the VP1 species of recombinant particles showed more VP1 species than those of the native virions from mouse cells, and an additional species of VP1 when VP2 was co-expressed with VP1. The recombinant particles were also compared for their ability to compete for polyomavirus infection. The competition assay indicated that the recombinant particles containing VP2 were the most efficient in inhibiting the native polyomavirus infection of 3T6 cells.

Animals↗

PubMed2000

A novel polyomavirus (goose hemorrhagic polyomavirus) is the agent of hemorrhagic nephritis enteritis of geese.

We have identified the etiological agent of hemorrhagic nephritis enteritis of geese (HNEG), a fatal disease of European geese. HNEG has been recognized in almost all goose breeding areas, with an epizootic pattern, and up to now, the infectious agent has remained unknown. In order to identify the causative agent, infected tissues from HNEG-affected geese were inoculated to 1-day-old goslings, which then developed clinical signs typical of HNEG. Tissue homogenates from these birds were subjected to Freon extraction followed by sucrose density gradient ultracentrifugation. The resulting main band was examined by electron microscopy and consisted of spherical, naked, papovavirus-like particles approximately 45 nm in diameter. The virus was isolated and propagated in goose kidney cell primary culture. Tissue- or culture-purified virus allowed the experimental reproduction of the disease in goslings. Random PCR amplification of viral nucleic acid produced a 1,175-bp fragment which was shown to be associated with field samples collected from geese affected by HNEG on commercial farms in France. Sequence analysis of the PCR product revealed a unique open reading frame, showing 63 to 72% amino acid similarity with the major capsid protein (VP1) of several polyomaviruses. Finally, based on phylogenetic analysis, we conclude that the causative agent of HNEG is closely related to but clearly distinct from other polyomaviruses; we thus have named this newly identified virus Goose hemorrhagic polyomavirus.

Amino Acid Sequence↗

PubMed2006

An outbreak of the polyomavirus infection in budgerigars and cockatiels in Slovakia, including a genome analysis of an avian polyomavirus isolate.

In winter 2003-04, large numbers of budgerigars (Mellopsitacus undulatus) and cockatiels (Nymphicus hollandicus) fell ill and died in a large parrot-breeding aviary in Slovakia. In budgerigars, the disease outbreak occurred at the age of 2-3 weeks; cockatiels died within their first 7 days of life. In budgerigars, symptoms of the disease included delayed growth, tremor, darkish discoloration of skin, quill bleeding, and feathering defects. cockatiels often died without any symptoms and with a full crop; feathering defects occurred sporadically. Electron microscopy with negative staining of aqueous lysates of the affected skin and of bleeding quills showed isolated or clustered polyomavirus particles 45-50 nm in size. Long filamentous forms of the virus were also found in virion clusters of skin lysates from the budgerigars. In ultrathin sections through the pathologically altered skin tissue of budgerigars, virus particles were present in both nuclei and cytoplasm of epidermal cells, often in crystalline form. In infected cells, enlarged nuclei showed an extensive chromatin margination. On the DNA level, presence of a polyomavirus infection was conclusively proved by the polymerase chain reaction using avian polyomavirus (APV)-specific primers. A sequence analysis of the gene encoding viral protein (VP)1 and of the combined region for VP2 and VP3 proteins revealed a previously undescribed synonymous mutation in this isolate. This report extended the knowledge of the area of APV occurrence and of the spectrum of hosts in the context of genomic and morphologic variability of APV isolates.

Animals↗

PubMed1994

Expression and purification of recombinant polyomavirus VP2 protein and its interactions with polyomavirus proteins.

Recombinant polyomavirus VP2 protein was expressed in Escherichia coli (RK1448), using the recombinant expression system pFPYV2. Recombinant VP2 was purified to near homogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, electroelution, and Extracti-Gel chromatography. Polyclonal serum to this protein which reacted specifically with recombinant VP2 as well as polyomavirus virion VP2 and VP3 on Western blots (immunoblots) was produced. Purified VP2 was used to establish an in vitro protein-protein interaction assay with polyomavirus structural proteins and purified recombinant VP1. Recombinant VP2 interacted with recombinant VP1, virion VP1, and the four virion histones. Recombinant VP1 coimmunoprecipitated with recombinant VP2 or truncated VP2 (delta C12VP2), which lacked the carboxy-terminal 12 amino acids. These experiments confirmed the interaction between VP1 and VP2 and revealed that the carboxyterminal 12 amino acids of VP2 and VP3 were not necessary for formation of this interaction. In vivo VP1-VP2 interaction study accomplished by cotransfection of COS-7 cells with VP2 and truncated VP1 (delta N11VP1) lacking the nuclear localization signal demonstrated that VP2 was capable of translocating delta N11VP1 into the nucleus. These studies suggest that complexes of VP1 and VP2 may be formed in the cytoplasm and cotransported to the nucleus for virion assembly to occur.

Animals↗

PubMed1989

Asp-286----Asn-286 in polyomavirus large T antigen relaxes the specificity of binding to the polyomavirus origin.

We isolated revertants of a polyomavirus whose origin of DNA replication contains a point mutation in the palindrome to which large T antigen binds. Four independent second-site revertants contain an Asp-286----Asn-286 substitution in large T antigen. This mutant large T antigen activates replication of DNAs containing the mutant polyomavirus origin as well as replication of DNAs containing the wild-type origin; however, replication of DNAs with enhancer mutations is not activated by this large T antigen. The Asn-286 mutation occurs in a positively charge region of large T antigen near the location of several mutations which inactivate DNA replication. We suggest that this region of large T antigen is responsible for recognition of specific DNA sequences at the origin and that ionic forces are important for this interaction.

Amino Acid Sequence↗

PubMed2003

Population-based study of antibody to the human polyomaviruses BKV and JCV and the simian polyomavirus SV40.

Molecular studies suggest that the simian polyomavirus SV40 is present in the human population, possibly introduced in contaminated polio vaccine. However, no recent seroepidemiological data exist in England on SV40 or on the two human polyomaviruses, BKV and JCV. A comparative age seroprevalence study was undertaken on 2,435 residual sera from 1991 by haemagglutination inhibition (HI) for BKV and JCV, and virus neutralisation for SV40. The overall rates of seropositivity for BKV and JCV were 81% and 35%, respectively, and each was significantly related to age (P < 0.001). BKV seroprevalence reached 91% at 5-9 years of age, but JCV seroprevalence reached only 50% by age 60-69 years. There was a highly significant association between BKV antibody titre and age (P < 0.001), titres decreasing linearly at a rate of 8.7% per 10 years (95% CI = 7.4-10% drop). Significantly more males than females had antibody to JCV (P = 0.013). In individuals under 40 years of age there was a significant negative association between the presence of antibody to BKV and JCV (P < 0.001). By contrast, the antibody prevalence to SV40 remained at 1.3-5% throughout all age groups and titres were low. There was a significant positive association between the presence of antibody to SV40 and antibody to both BKV (P < 0.001) and JCV (P = 0.009), and also to the geometric mean titre (GMT) of BKV antibody (P = 0.011). The results indicate that BKV and JCV are transmitted by different routes. There is no serological evidence that SV40 entered the human population during the past 80 years, and the possibility of cross-reaction with BKV or JCV antibody must be considered.

Adolescent↗

PubMed1983

Structural analysis of integrated polyomavirus DNA in a polyomavirus-induced hamster tumor cell line.

The nucleotide sequence and structural organization of integrated polyomavirus DNA and flanking host chromosomal DNA in a polyomavirus-induced hamster tumor cell line were evaluated. Although the proximal portion of the early transcriptional region was intact, the remainder of the integrated viral sequences was characterized by a series of rearrangements, including deletions, insertions, and a tandem duplication. Short direct repeats of different nucleotide sequences located on each side of the host-viral DNA junctions we examined were observed. Tumor cell chromosomal DNA flanking the integration site contained regions of patchy homology with viral DNA sequences which could have participated in the recombinational events leading to stable integration. The presence of several unusual structural features of tumor cell chromosomal DNA at the site of viral DNA integration, which were reminiscent of papovavirus DNA integrated into transformed cells, suggests that the recombinational mechanisms operative in vivo are accurately reflected by those functioning in vitro.

Animals↗

PubMed1984

Multiple binding sites for polyomavirus large T antigen within regulatory sequences of polyomavirus DNA.

Polyomavirus large T antigen binds specifically to multiple sites within the regulatory region of the viral genome. Experiments done with crude extracts from wild-type virus-infected mouse cells and immunoprecipitation of protein-DNA complexes localized two high-affinity binding sites on the early region side of the DNA replication origin. Purification of the large T antigen by immunoaffinity chromatography made it possible to refine the analysis through application of DNase I footprinting. The high-affinity interactions were resolved into three closely spaced, but distinct, binding regions. These begin at a site only slightly overlapping the early boundary of the core replication origin, a location highly homologous to that of simian virus 40 large T antigen-binding site I, but then extend away from the origin toward the early coding sequence and thus span the early region transcriptional initiation sites. Each tight-binding region contains from two to four copies of the sequence 5'-(A = T)G(A greater than G)GGC-3' repeated at 9- to 11-base-pair spacing. At high protein concentrations and at low ionic strength, additional sites within the core replication origin and in the enhancer region were protected from DNase I digestion. These minor binding sites also included repeats of sequences related to the consensus, but at different spacings. Our results suggest that, unlike simian virus 40 DNA, the polyomavirus genome may have distinct regions of interaction with its large T antigen which separately are involved in initiation of DNA replication and the regulation of viral transcription.

Antigens, Viral, Tumor↗

PubMed1998

Cytologic and genetic study of polyomavirus-infected or polyomavirus-activated cells in human urine.

OBJECTIVE: To carry out a morphologic and genetic study of human polyomavirus infection or activation in child and adult urine specimens. DESIGN AND SETTING: The study was carried out on 16 urine samples from children with human polyomavirus infection and 104 samples from adults with virus activation identified among 18800 consecutive urine samples (0.64%). RESULTS: All specimens from children showed numerous typical intranuclear inclusion-bearing (INIB) cells. All adult specimens with cytological features similar to childhood specimens were defined as type 1 adult cases. We identified 14 adult cases with marked immunologic suppression as type 1 cases. The inclusions were large, homogeneous, and basophilic, and they were mainly attributable to the BK virus, as demonstrated by a polymerase chain reaction. These infected or activated cells revealed features demonstrating their origin in the superficial transitional epithelium of the urinary tract. Adult cases with different cytologic features were designated as type 2 adult cases. In type 2 adult cases, the number of virus-activated cells was lower, and degenerated intranuclear inclusion-bearing cells with a coarse chromatin pattern were observed in most cases. These characteristics were identified in 90 adults without immunologic suppression. A polymerase chain reaction with BamHI digestion demonstrated JC virus DNA in nearly all of these specimens. CONCLUSION: The JC virus-activated cells found in type 2 adult cases and the BK virus-infected cells found in childhood cases were not of clinical importance. However, the BK virus-activated cells associated with immunologic suppression may have prognostic significance.

Adult↗

PubMed2026

Binding capacity of Intravenous immunoglobulin G to BK polyomavirus determines its anti-BK polyomavirus activity in infected cultures.

BK polyomavirus (BKPyV) causes disease in immunocompromised individuals. This study tested the hypothesis that the antiviral efficacy of intravenous immunoglobulin (IVIG) against BKPyV depends on the relationship between its virus-binding capacity and the viral burden. We first quantified the BKPyV-binding capacity of IVIG and then characterized BKPyV replication in kidney-derived HK-2 and HEK293 cells and in HEL cells under IVIG treatment. Subsequently, we analyzed the efficacy of IVIG at 0.03-10 mg/mL against low-multiplicity of infection (MOI) and high-MOI infection in relation to the BKPyV-binding capacity of IVIG. BKPyV productively infected all three cell lines, with 14-day replication cycles of 2.2, 4.0, and 7.0 in HK-2, HEK293, and HEL cells, respectively, indicating that HEL cells were the most permissive. IVIG bound approximately 108 copies of BKPyV DNA per milligram. In the low-MOI infection model, where the total viral load remained within this estimated binding capacity, IVIG showed clear neutralizing activity, significantly reducing viral spread, viral DNA levels, and the number of VP1-positive cells in a dose-dependent manner (p < 0.001). In contrast, in the high-MOI infection model, the viral load appeared to be high relative to the estimated IVIG binding capacity even at 10 mg/mL, and IVIG showed little or no neutralizing effect on viral production or spread of infected cells. These findings identify an experimental relationship between IVIG binding capacity, viral burden, and antiviral efficacy and suggest that the antiviral effect of IVIG is greatest when administered early, thereby supporting further clinical evaluation of early or preemptive IVIG administration.

Humans↗

PubMedDate not supplied

Murine polyomavirus-VP1 virus-like particles immunize against some polyomavirus-induced tumours.

The ability of murine polyomavirus (MPyV)-VP1 virus-like particles (MPyV-VLPs) to immunize against MPyV tumour outgrowth was investigated. Non-immunized and mice immunized three times were challenged with MPyV or non-MPyV tumours and followed for tumour outgrowth. MPyV-VLP immunization abrogated outgrowth of some, but not all, tested MPyV tumours and delayed the outgrowth of a non-MPyV tumour to some extent. However, when mice were irradiated prior to tumour challenge to avoid an unspecific immune response, protection was MPyV-specific. In conclusion, VLP immunization for prevention of viral infection could also contribute to immune-protection against some tumours induced by the corresponding virus.

Animals↗

PubMed1983

Comparison of the DNA sequence of the Crawford small-plaque variant of polyomavirus with those of polyomaviruses A2 and strain 3.

The DNA sequence of two wild-type strains of polyomavirus (A2 and strain 3) are known. We have determined the majority of the DNA sequence of a third strain, the Crawford small-plaque virus. This virus has been noted for its capacity to induce readily detected tumor-specific transplantation antigen in hamster cells, a property that is most likely attributable to an altered middle T-antigen. A comparison of its DNA sequence with those of the A2 and strain 3 viruses reveals numerous nucleotide substitutions, insertions, and deletions throughout the genome. Most sequence changes in coding regions are silent mutations; however, variability in proteins can be predicted from these sequence data at 5 locations in middle T-antigen, 10 in large T-antigen, and 10 in VP1. The Crawford small-plaque virus noncoding regulatory region contains, in addition to nucleotide substitutions, a 44-base-pair tandem repeat of sequences on the late side of the origin of DNA replication.

Antigens, Viral, Tumor↗

PubMed1989

Polyomavirus genome and polyomavirus enhancer-driven gene expression during myogenesis.

The mRNAs for myogenic functions are coordinately transcribed with polyomavirus (Py) early mRNA during in vitro differentiation of mouse C2 myoblast cells. Sequence analysis shows that the A domain of the Py enhancer includes an E1A-like consensus sequence that is also found in the 5' upstream region of two genes expressed during myoblast differentiation: alpha-actin and myosin light chain. Therefore, the coordinate expression of such genes with Py early mRNA may be activated by a common cellular regulatory factor. In the present work, we report that C2 cells surviving Py infection are unable to differentiate and do not express alpha-actin and myosin light-chain mRNAs. Hybrids between such Py-resistant myoblast cells and the parental cells exhibited dominance of the permissibility to Py growth and of the expression of myogenic mRNAs. In C2 cells transiently transfected with a chimeric plasmid (pSVPy12CAT) harboring the bacterial chloramphenicol acetyltransferase (CAT) gene driven by the Py enhancer-promoter region, the CAT gene was expressed irrespective of their stage of differentiation. Moreover, undifferentiated stably transfected cells expressing the CAT gene restricted viral growth. Py-resistant C2 myoblasts transiently transfected with pSVPy12CAT also expressed the CAT gene driven by the Py enhancer. This contradictory finding is similar to results previously obtained by other investigators with cloned genes specific for myogenic functions, and it may be explained by a structural difference between the pSVPy12CAT and the Py genomic organizations in which the viral enhancer operates.

Animals↗

PubMed1992

Induction of polyomavirus DNA replication by carcinogens in polyomavirus-transformed rat cells: evidence that the viral enhancer is not the primary target in the induction pathway.

In the polyomavirus (Py)-transformed rat cell line designated LPT, replication of the integrated Py DNA can be induced by exposure of the cells to carcinogens. In view of the observation that enhancer elements are essential components of the Py origin of replication, it appeared plausible that the induction is triggered by synthesis or modification of an enhancer-binding protein which is required for activation of the viral origin. To test this hypothesis, we have used a plasmid containing a modified Py origin (test plasmid), in which the Py enhancer has been replaced with five repeats of the yeast GAL4 upstream activating sequence, and a plasmid encoding the GAL4 transcriptional activator protein. Previous studies in which these two plasmids were cotransfected into mouse cells that are permissive for Py showed that the GAL4 protein can transactivate the modified Py origin and cause replication of the test plasmid. When similar cotransfection assays were performed in LPT cells, no replication of the test plasmid was observed unless the cells were exposed to the carcinogen mitomycin C subsequent to the transfection, in which case replication of the test plasmid was induced. Control experiments showed that even though the GAL4 protein was required for the induction, its concentration was not affected by the exposure to mitomycin C. These results indicate that the primary target in the induction pathway is not an enhancer-binding protein; instead, the induction appears to be triggered by changes in other components of the replication initiation complex which may be associated with the origin core.

Animals↗